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Age-Dependent Reduction in Asthmatic Pathology through Reprogramming of Postviral Inflammatory Responses.
Hazan, Guy; Eubanks, Anna; Gierasch, Carrie; Atkinson, Jeffrey; Fox, Carolyn; Hernandez-Leyva, Ariel; Rosen, Anne L; Kau, Andrew L; Agapov, Eugene; Alexander-Brett, Jennifer; Steinberg, Deborah; Kelley, Diane; White, Michael; Byers, Derek; Wu, Kangyun; Keeler, Shamus P; Zhang, Yong; Koenitzer, Jeffrey R; Eiden, Elise; Anderson, Neil; Holtzman, Michael J; Haspel, Jeffrey.
  • Hazan G; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO.
  • Eubanks A; Division of Pediatric Allergy and Pulmonary Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.
  • Gierasch C; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO.
  • Atkinson J; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO.
  • Fox C; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO.
  • Hernandez-Leyva A; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO.
  • Rosen AL; Division of Allergy and Immunology, Department of Medicine and Center for Women's Infectious Disease Research, Washington University School of Medicine, St. Louis, MO.
  • Kau AL; Division of Allergy and Immunology, Department of Medicine and Center for Women's Infectious Disease Research, Washington University School of Medicine, St. Louis, MO.
  • Agapov E; Division of Allergy and Immunology, Department of Medicine and Center for Women's Infectious Disease Research, Washington University School of Medicine, St. Louis, MO.
  • Alexander-Brett J; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO.
  • Steinberg D; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO.
  • Kelley D; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO.
  • White M; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO.
  • Byers D; Department of Pathology/Immunology, Washington University School of Medicine, St. Louis, MO.
  • Wu K; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO.
  • Keeler SP; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO.
  • Zhang Y; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO.
  • Koenitzer JR; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO.
  • Eiden E; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO.
  • Anderson N; Institute for Informatics, Washington University School of Medicine, St. Louis, MO; and.
  • Holtzman MJ; Division of Laboratory and Genomic Medicine, Department of Pathology, Washington University School of Medicine, St. Louis, MO.
  • Haspel J; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO.
J Immunol ; 208(6): 1467-1482, 2022 03 15.
Article in English | MEDLINE | ID: covidwho-1690085
ABSTRACT
Asthma is a chronic disease of childhood, but for unknown reasons, disease activity sometimes subsides as children mature. In this study, we present clinical and animal model evidence suggesting that the age dependency of childhood asthma stems from an evolving host response to respiratory viral infection. Using clinical data, we show that societal suppression of respiratory virus transmission during coronavirus disease 2019 lockdown disrupted the traditional age gradient in pediatric asthma exacerbations, connecting the phenomenon of asthma remission to virus exposure. In mice, we show that asthmatic lung pathology triggered by Sendai virus (SeV) or influenza A virus is highly age-sensitive robust in juvenile mice (4-6 wk old) but attenuated in mature mice (>3 mo old). Interestingly, allergen induction of the same asthmatic traits was less dependent on chronological age than viruses. Age-specific responses to SeV included a juvenile bias toward type 2 airway inflammation that emerged early in infection, whereas mature mice exhibited a more restricted bronchiolar distribution of infection that produced a distinct type 2 low inflammatory cytokine profile. In the basal state, aging produced changes to lung leukocyte burden, including the number and transcriptional landscape of alveolar macrophages (AMs). Importantly, depleting AMs in mature mice restored post-SeV pathology to juvenile levels. Thus, aging influences chronic outcomes of respiratory viral infection through regulation of the AM compartment and type 2 inflammatory responses to viruses. Our data provide insight into how asthma remission might develop in children.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Influenza A virus / Respirovirus Infections / Asthma / Aging / Age Factors / Orthomyxoviridae Infections / Th2 Cells / Sendai virus / Influenza, Human / SARS-CoV-2 Type of study: Observational study / Prognostic study Limits: Animals / Humans Country/Region as subject: North America Language: English Journal: J Immunol Year: 2022 Document Type: Article Affiliation country: Jimmunol.2101094

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Influenza A virus / Respirovirus Infections / Asthma / Aging / Age Factors / Orthomyxoviridae Infections / Th2 Cells / Sendai virus / Influenza, Human / SARS-CoV-2 Type of study: Observational study / Prognostic study Limits: Animals / Humans Country/Region as subject: North America Language: English Journal: J Immunol Year: 2022 Document Type: Article Affiliation country: Jimmunol.2101094